Considerable evidence indicates that the chronic synovitis in rheumatoid arthritis is immunologically mediated. Recent observations in this laboratory have identified a unique self-association of IgG-rheumatoid factors. During the proposed work, immune complexes will be purified from the synovial fluid of patients with rheumatoid arthritis by gel filtration and affinity chromatography. The presence or absence of self-associating IgG-rheumatoid factors will be established in these immune complexes. The potential role of self-associated IgG-rheumatoid factors in generation of inflammation will be determined. Methods will be developed and evaluated for detection of IgG-rheumatoid factors in synovial fluid and serum samples. The self-association of IgG-rheumatoid factors may constitute the major antigen-antibody system responsible for maintaining the chronic synovitis in rheumatoid arthritis.